Oropharyngeal cancer is uncommon. Worldwide, cancers of the oropharynx and hypopharynx account for an estimated 123,000 new cases per year, with an estimated mortality of 79,000 deaths.[1] Typically, oropharyngeal cancer involves patients in the fifth through seventh decades of life; men are afflicted 3 to 5 times more often than women.[1-3]

Similar to other cancers of the head and neck, tobacco and alcohol abuse represent the most significant risk factors for the development of oropharyngeal cancer.[3,4] (Refer to the PDQ summaries on Hypopharyngeal Cancer Treatment and Lip and Oral Cavity Cancer Treatment for more information.) Other risk factors may include:[5]

• A diet poor in fruits and vegetables.[6]
• The consumption of maté, a stimulant beverage commonly consumed in South America.[7]
• The chewing of betel quid, a stimulant preparation commonly used in parts of Asia.[8]
• Infection with the human papillomavirus (HPV), especially HPV-type-16, also known as HPV-16.[9,10]

Defective elimination of acetaldehyde, a carcinogen generated by alcohol metabolism, poses an additional risk factor for oropharyngeal cancers. In individuals, primarily East Asians, carrying an inactive mutant allele of alcohol dehydrogenase-2, alcohol consumption is associated with a susceptibility to multiple metachronous oropharyngeal cancers that are caused by the decreased elimination of acetaldehyde.[11]

Anatomically, the oropharynx is located between the soft palate superiorly and the hyoid bone inferiorly; it is continuous with the oral cavity anteriorly and communicates with the nasopharynx superiorly and the supraglottic larynx and hypopharynx inferiorly. The oropharynx is divided into the following sites:[12]

• Base of the tongue, which includes the pharyngoepiglottic folds and the glossoepiglottic folds.
• Tonsillar region, which includes the fossa and the anterior and posterior pillars.
• Soft palate, which includes the uvula.
• Pharyngeal walls, that is, posterior and lateral.

The regional lymph node anatomy of the head and neck contains lymph nodes that run parallel to the jugular veins, spinal accessory nerve, and facial artery and into the submandibular triangle; an understanding of this anatomy and the status of regional lymph nodes is critical to the care of head and neck cancer patients.[3,13] The regions of the neck have been characterized by levels (I–V) to facilitate communication regarding the lymph node anatomy:

• Level I contains the submental and submandibular lymph nodes.
• Level II contains the upper jugular lymph nodes, which are above the digastric muscle.
• Level III contains the mid-jugular lymph nodes, which are between the omohyoid muscle and the digastric muscle.
• Level IV contains the lower jugular lymph nodes.
• Level V contains the lymph nodes of the posterior triangle.

Histologically, almost all oropharyngeal cancers are squamous cell carcinomas (SCCs).[3] Other cancers in this area include minor salivary gland carcinomas, lymphomas, and lymphoepitheliomas, also known as tonsillar fossa. (Refer to the PDQ summaries on Salivary Gland Cancer Treatment, Adult Hodgkin Lymphoma Treatment, and Adult Non-Hodgkin Lymphoma Treatment for more information.)

The concept of field cancerization may be responsible in part for the multiple, synchronous primary SCCs that occur in oropharyngeal cancer. This concept, originally described in 1953, proposes that tumors develop in a multifocal fashion within a field of tissue chronically exposed to carcinogens.[14] Molecular studies detecting genetic alterations in histologically normal tissue from high-risk individuals have provided strong support for the field cancerization concept.[15-19]

Clinically, cancers of the base of the tongue are insidious. These cancers can grow in either an infiltrative or exophytic pattern. Because the base of the tongue is devoid of pain fibers, these tumors are often asymptomatic until they have progressed significantly.[12] Symptoms may include pain, dysphagia, weight loss, referred otalgia secondary to cranial nerve involvement, trismus secondary to pterygoid muscle involvement, fixation of the tongue that is caused by infiltration of the deep muscle, and a mass in the neck.[3,12] (Refer to the PDQ Pain summary and for more information on weight loss, refer to the Nutrition in Cancer Care summary.) Lymph node metastasis is common because of the rich lymphatic drainage of the base of the tongue. Approximately 70% or more of the patients have ipsilateral cervical nodal metastases; 30% or fewer of the patients have bilateral cervical lymph node metastases.[12,20] The cervical lymph nodes involved commonly include levels II and III.

The symptoms of tonsillar lesions include pain, dysphagia, weight loss, ipsilateral referred otalgia, and a mass in the neck.[3,12] The anterior tonsillar pillar and tonsil is the most common location for a primary tumor of the oropharynx.[12] Lesions involving the anterior tonsillar pillar may appear as areas of dysplasia, inflammation, or a superficial spreading lesion. These cancers can progress across a broad region including the lateral soft palate, retromolar trigone and buccal mucosa, and tonsillar fossa.[3,12] The lymphatic drainage is primarily to level II nodes.

Lesions of the tonsillar fossa may be either exophytic or ulcerative and have a pattern of extension similar to those of the anterior tonsillar pillar. These tumors present in advanced-stage disease more often than cancers of the tonsillar pillar. Approximately 75% of patients will present with stage III or stage IV disease.[3,12] The lymphatic drainage is primarily to level V nodes. Tumors of the posterior tonsillar pillar can extend inferiorly to involve the pharyngoepiglottic fold and the posterior aspect of the thyroid cartilage. These lesions more frequently involve level V nodes.

Soft palate tumors are primarily found on the anterior surface.[12] Lesions in this area may remain superficial and in early stages.[3] The lymphatic drainage is primarily to level II nodes.

Tumors of the pharyngeal wall are typically diagnosed in an advanced stage because of the silent location in which they develop.[3,12] Symptoms may include pain, bleeding, weight loss, and a neck mass. These lesions can spread superiorly to involve the nasopharynx, posteriorly to infiltrate the prevertebral fascia, and inferiorly to involve the pyriform sinuses and hypopharyngeal walls. Primary lymphatic drainage is to the retropharyngeal nodes and level II and III nodes. Because most pharyngeal tumors extend past the midline, bilateral cervical metastases are common.

Precancerous lesions of the oropharynx include leukoplakia, erythroplakia, and mixed erythroleukoplakia.[5] These are clinical terms that have no specific histopathologic connotations.[21] Leukoplakia, the most common of the three conditions, is defined by the World Health Organization as “a white patch or plaque that cannot be characterized clinically or pathologically as any other disease.”[22] The diagnosis of leukoplakia is one of exclusion; conditions such as candidiasis, lichen planus, leukoedema, and others must be ruled out before a diagnosis of leukoplakia can be made.[5]

The prevalence of leukoplakia in the United States is decreasing; this decline has been related to a reduction of tobacco consumption.[23] Although erythroplakia is not as common as leukoplakia, it is much more likely to be associated with dysplasia or carcinoma.[5,24]

The clinical anatomic staging of oropharyngeal cancers involves both clinical assessment and imaging techniques.[3,13] One study has reported that positron emission tomography scans are more accurate than computed tomographic scans or magnetic resonance imaging in detecting occult nodal disease.[25] Diagnostic methods under development involve the molecular analysis of tissue from the margins of lip and oral cavity SCCs (i.e., molecular staging) to detect tumor-associated genetic alterations in cells that appear normal by conventional light microscopy. Molecular staging may predict the likelihood of recurrence and may help to establish the relationship between index lesions of SCCs and subsequent lesions.[26,27]

Traditionally, surgery and/or radiation therapy have been the standards for treatment of oropharyngeal cancers; these treatment modalities are frequently complicated by suboptimal control of locoregional disease and significant long-term functional deficits.[3,28] Although specific indications for primary surgical resection exist, some investigators suggest that the concurrent use of multiagent chemotherapy and radiation has become the standard of care for the management of patients with late-stage disease, and surgery is often reserved for salvage of those patients who fail definitive nonoperative treatment.[26,28,29] Studies using aggressive and uncompromised radiation therapy with concurrent multiagent chemotherapy have consistently demonstrated a survival and locoregional control benefit.[30-34] This treatment approach emphasizes organ preservation and functionality. New treatments under development include various biologic therapies (i.e., vaccines, growth factor-receptor antagonists, cyclin-dependent kinase inhibitors, oncolytic viruses, and others) and photodynamic therapy.[26,35-42]

The rate of curability of cancers of the oropharynx varies depending on the stage and specific site. Local control rates for early base-of-tongue cancers approximate 85%.[3] In a large retrospective study involving 262 patients with base-of-tongue cancer, the overall 5-year disease-specific survival rate for patients with all stages of disease was approximately 50%. Treatment modalities included surgery with and without radiation therapy and radiation therapy alone. None of the treatment modalities had a significant survival advantage either overall or within the stages.[43,44]

In a retrospective study involving 162 patients with tonsil carcinoma, 84 patients were treated with primary surgery, which was followed by radiation therapy and/or chemotherapy if histologic signs of aggressive behavior were identified. Survival rates were 89% for stage I, 91% for stage II, 79% for stage III, and 52% for stage IV.[45] In a retrospective study of 188 patients with SCC of the soft palate, uvula, and anterior tonsillar pillar, treatment to the primary site consisted of radiation therapy for 150 patients, surgery for 28 patients, and combined therapy for 10 patients. The overall determinant survival was 80% at 2 years, but it fell to 67% at 5 years.[46] In another retrospective study, 148 patients received definitive radiation therapy for SCC of the pharyngeal wall. Cause-specific survival rates were 89% for stage I, 88% for stage II, 44% for stage III, and 34% for stage IV. Twice-daily fractionation, stage I to stage II disease, and an oropharyngeal primary site were associated with improved locoregional control.[47]

HPV-positive oropharyngeal cancers may represent a distinct disease entity that is causally associated with HPV infection and that is also associated with an improved prognosis. Several studies indicate that individuals with HPV-positive tumors have significantly improved survivals.[10,48,49] In a prospective study involving 253 patients with newly diagnosed or recurrent head and neck SCC, HPV was detected in 25% of the cases. Poor tumor grade and an oropharyngeal site independently increased the probability of HPV presence.[10]

The risk of developing a second primary tumor in patients with tumors of the upper aerodigestive tract has been estimated to be 3% to 7% per year.[50,51] Because of this risk, surveillance of these patients should be lifelong. Patients should be counseled that continued smoking and alcohol consumption after treatment has been associated with the development of second primary tumors of the aerodigestive tract.[52-54] (Refer to the PDQ Smoking Cessation and Continued Risk in Cancer Patients summary for more information.)

To date, SCC of the oropharynx has not been associated with any specific chromosomal or genetic abnormalities. Genetic/chromosomal aberrations in these cancers are complex.[55,56] Despite the lack of specific genetic abnormalities, testing for genetic alterations or ploidy in early oropharyngeal lesions may identify patients who are at the greatest risk for progression and may lead to more definitive therapy.[26]

References

1. Parkin DM, Bray F, Ferlay J, et al.: Estimating the world cancer burden: Globocan 2000. Int J Cancer 94 (2): 153-6, 2001.  [PUBMED Abstract]
   
   
2. American Cancer Society.: Cancer Facts and Figures 2004. Atlanta, Ga: American Cancer Society, 2004. Also available online. Last accessed January 21, 2008. 
   
   
3. Mendenhall WM, Riggs CE Jr, Cassisi NJ: Treatment of head and neck cancers. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 662-732. 
   
   
4. Licitra L, Bernier J, Grandi C, et al.: Cancer of the oropharynx. Crit Rev Oncol Hematol 41 (1): 107-22, 2002.  [PUBMED Abstract]
   
   
5. Neville BW, Day TA: Oral cancer and precancerous lesions. CA Cancer J Clin 52 (4): 195-215, 2002 Jul-Aug.  [PUBMED Abstract]
   
   
6. Sánchez MJ, Martínez C, Nieto A, et al.: Oral and oropharyngeal cancer in Spain: influence of dietary patterns. Eur J Cancer Prev 12 (1): 49-56, 2003.  [PUBMED Abstract]
   
   
7. Goldenberg D, Golz A, Joachims HZ: The beverage maté: a risk factor for cancer of the head and neck. Head Neck 25 (7): 595-601, 2003.  [PUBMED Abstract]
   
   
8. Ho PS, Ko YC, Yang YH, et al.: The incidence of oropharyngeal cancer in Taiwan: an endemic betel quid chewing area. J Oral Pathol Med 31 (4): 213-9, 2002.  [PUBMED Abstract]
   
   
9. Mork J, Lie AK, Glattre E, et al.: Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med 344 (15): 1125-31, 2001.  [PUBMED Abstract]
   
   
10. Gillison ML, Koch WM, Capone RB, et al.: Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92 (9): 709-20, 2000.  [PUBMED Abstract]
    
    
11. Yokoyama A, Watanabe H, Fukuda H, et al.: Multiple cancers associated with esophageal and oropharyngolaryngeal squamous cell carcinoma and the aldehyde dehydrogenase-2 genotype in male Japanese drinkers. Cancer Epidemiol Biomarkers Prev 11 (9): 895-900, 2002.  [PUBMED Abstract]
    
    
12. Hu KS, Harrison LB, Culliney B, et al.: Cancer of the oropharynx. In: Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. 2nd ed. Philadelphia Pa: Lippincott Williams & Wilkins, 2004, pp 306-51. 
    
    
13. Pharynx (including base of tongue, soft palate and uvula). In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 31-46. 
    
    
14. Slaughter DP, Southwick HW, Smejkal W: Field cancerization in oral stratified squamous epithelium: clinical implications of multicentric origin. Cancer 6 (5): 963-8, 1953. 
    
    
15. Braakhuis BJ, Tabor MP, Leemans CR, et al.: Second primary tumors and field cancerization in oral and oropharyngeal cancer: molecular techniques provide new insights and definitions. Head Neck 24 (2): 198-206, 2002.  [PUBMED Abstract]
    
    
16. Braakhuis BJ, Tabor MP, Kummer JA, et al.: A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. Cancer Res 63 (8): 1727-30, 2003.  [PUBMED Abstract]
    
    
17. Tabor MP, Brakenhoff RH, van Houten VM, et al.: Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 7 (6): 1523-32, 2001.  [PUBMED Abstract]
    
    
18. Tabor MP, Brakenhoff RH, Ruijter-Schippers HJ, et al.: Multiple head and neck tumors frequently originate from a single preneoplastic lesion. Am J Pathol 161 (3): 1051-60, 2002.  [PUBMED Abstract]
    
    
19. Ha PK, Califano JA: The molecular biology of mucosal field cancerization of the head and neck. Crit Rev Oral Biol Med 14 (5): 363-9, 2003.  [PUBMED Abstract]
    
    
20. Lindberg R: Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer 29 (6): 1446-9, 1972.  [PUBMED Abstract]
    
    
21. Oral cavity and oropharynx. In: Rosai J, ed.: Ackerman's Surgical Pathology. 8th ed. St. Louis, Mo: Mosby, 1996, pp 223-55. 
    
    
22. Kramer IR, Lucas RB, Pindborg JJ, et al.: Definition of leukoplakia and related lesions: an aid to studies on oral precancer. Oral Surg Oral Med Oral Pathol 46 (4): 518-39, 1978.  [PUBMED Abstract]
    
    
23. Scheifele C, Reichart PA, Dietrich T: Low prevalence of oral leukoplakia in a representative sample of the US population. Oral Oncol 39 (6): 619-25, 2003.  [PUBMED Abstract]
    
    
24. Shafer WG, Waldron CA: Erythroplakia of the oral cavity. Cancer 36 (3): 1021-8, 1975.  [PUBMED Abstract]
    
    
25. Ng SH, Yen TC, Chang JT, et al.: Prospective study of [18F]fluorodeoxyglucose positron emission tomography and computed tomography and magnetic resonance imaging in oral cavity squamous cell carcinoma with palpably negative neck. J Clin Oncol 24 (27): 4371-6, 2006.  [PUBMED Abstract]
    
    
26. Forastiere A, Koch W, Trotti A, et al.: Head and neck cancer. N Engl J Med 345 (26): 1890-900, 2001.  [PUBMED Abstract]
    
    
27. Brennan JA, Mao L, Hruban RH, et al.: Molecular assessment of histopathological staging in squamous-cell carcinoma of the head and neck. N Engl J Med 332 (7): 429-35, 1995.  [PUBMED Abstract]
    
    
28. Adelstein DJ: Oropharyngeal cancer: the role of chemotherapy. Curr Treat Options Oncol 4 (1): 3-13, 2003.  [PUBMED Abstract]
    
    
29. Forastiere AA, Trotti A: Radiotherapy and concurrent chemotherapy: a strategy that improves locoregional control and survival in oropharyngeal cancer. J Natl Cancer Inst 91 (24): 2065-6, 1999.  [PUBMED Abstract]
    
    
30. Adelstein DJ, Saxton JP, Lavertu P, et al.: A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. Head Neck 19 (7): 567-75, 1997.  [PUBMED Abstract]
    
    
31. Wendt TG, Grabenbauer GG, Rödel CM, et al.: Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. J Clin Oncol 16 (4): 1318-24, 1998.  [PUBMED Abstract]
    
    
32. Brizel DM, Albers ME, Fisher SR, et al.: Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 338 (25): 1798-804, 1998.  [PUBMED Abstract]
    
    
33. Denis F, Garaud P, Bardet E, et al.: Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 22 (1): 69-76, 2004.  [PUBMED Abstract]
    
    
34. Staar S, Rudat V, Stuetzer H, et al.: Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 50 (5): 1161-71, 2001.  [PUBMED Abstract]
    
    
35. Chang AE, Li Q, Jiang G, et al.: Generation of vaccine-primed lymphocytes for the treatment of head and neck cancer. Head Neck 25 (3): 198-209, 2003.  [PUBMED Abstract]
    
    
36. Mendelsohn J, Baselga J: Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 21 (14): 2787-99, 2003.  [PUBMED Abstract]
    
    
37. Senderowicz AM: Novel direct and indirect cyclin-dependent kinase modulators for the prevention and treatment of human neoplasms. Cancer Chemother Pharmacol 52 (Suppl 1): S61-73, 2003.  [PUBMED Abstract]
    
    
38. Chiocca EA: Oncolytic viruses. Nat Rev Cancer 2 (12): 938-50, 2002.  [PUBMED Abstract]
    
    
39. Copper MP, Tan IB, Oppelaar H, et al.: Meta-tetra(hydroxyphenyl)chlorin photodynamic therapy in early-stage squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 129 (7): 709-11, 2003.  [PUBMED Abstract]
    
    
40. Biel MA: Photodynamic therapy and the treatment of head and neck neoplasia. Laryngoscope 108 (9): 1259-68, 1998.  [PUBMED Abstract]
    
    
41. Lou PJ, Jones L, Hopper C: Clinical outcomes of photodynamic therapy for head-and-neck cancer. Technol Cancer Res Treat 2 (4): 311-7, 2003.  [PUBMED Abstract]
    
    
42. Hopper C: Photodynamic therapy: a clinical reality in the treatment of cancer. Lancet Oncol 1: 212-9, 2000.  [PUBMED Abstract]
    
    
43. Sessions DG, Lenox J, Spector GJ, et al.: Analysis of treatment results for base of tongue cancer. Laryngoscope 113 (7): 1252-61, 2003.  [PUBMED Abstract]
    
    
44. Mendenhall WM, Morris CG, Amdur RJ, et al.: Definitive radiotherapy for squamous cell carcinoma of the base of tongue. Am J Clin Oncol 29 (1): 32-9, 2006.  [PUBMED Abstract]
    
    
45. Galati LT, Myers EN, Johnson JT: Primary surgery as treatment for early squamous cell carcinoma of the tonsil. Head Neck 22 (3): 294-6, 2000.  [PUBMED Abstract]
    
    
46. Weber RS, Peters LJ, Wolf P, et al.: Squamous cell carcinoma of the soft palate, uvula, and anterior faucial pillar. Otolaryngol Head Neck Surg 99 (1): 16-23, 1988.  [PUBMED Abstract]
    
    
47. Hull MC, Morris CG, Tannehill SP, et al.: Definitive radiotherapy alone or combined with a planned neck dissection for squamous cell carcinoma of the pharyngeal wall. Cancer 98 (10): 2224-31, 2003.  [PUBMED Abstract]
    
    
48. Ringström E, Peters E, Hasegawa M, et al.: Human papillomavirus type 16 and squamous cell carcinoma of the head and neck. Clin Cancer Res 8 (10): 3187-92, 2002.  [PUBMED Abstract]
    
    
49. Schwartz SR, Yueh B, McDougall JK, et al.: Human papillomavirus infection and survival in oral squamous cell cancer: a population-based study. Otolaryngol Head Neck Surg 125 (1): 1-9, 2001.  [PUBMED Abstract]
    
    
50. Khuri FR, Lippman SM, Spitz MR, et al.: Molecular epidemiology and retinoid chemoprevention of head and neck cancer. J Natl Cancer Inst 89 (3): 199-211, 1997.  [PUBMED Abstract]
    
    
51. León X, Quer M, Diez S, et al.: Second neoplasm in patients with head and neck cancer. Head Neck 21 (3): 204-10, 1999.  [PUBMED Abstract]
    
    
52. Do KA, Johnson MM, Doherty DA, et al.: Second primary tumors in patients with upper aerodigestive tract cancers: joint effects of smoking and alcohol (United States). Cancer Causes Control 14 (2): 131-8, 2003.  [PUBMED Abstract]
    
    
53. Khuri FR, Kim ES, Lee JJ, et al.: The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial. Cancer Epidemiol Biomarkers Prev 10 (8): 823-9, 2001.  [PUBMED Abstract]
    
    
54. Day GL, Blot WJ, Shore RE, et al.: Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. J Natl Cancer Inst 86 (2): 131-7, 1994.  [PUBMED Abstract]
    
    
55. Tremmel SC, Götte K, Popp S, et al.: Intratumoral genomic heterogeneity in advanced head and neck cancer detected by comparative genomic hybridization. Cancer Genet Cytogenet 144 (2): 165-74, 2003.  [PUBMED Abstract]
    
    
56. Brieger J, Jacob R, Riazimand HS, et al.: Chromosomal aberrations in premalignant and malignant squamous epithelium. Cancer Genet Cytogenet 144 (2): 148-55, 2003.  [PUBMED Abstract]
    
    

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